Zedira’s lead indication is celiac disease. Celiac disease is the most common chronic inflammation of the small intestine. The autoimmune disease affects up to 2% of most populations and is caused by nutritional gluten in genetically predisposed individuals. A key step in celiac disease pathogenesis is gluten-deamidation and immunogenic potentiation catalyzed by the patient’s own tissue transglutaminase in the gut.
The small molecule ZED12271
targets the dysregulated transglutaminase within the small intestine, to prevent the immune response to transglutaminase-modified gluten which drives the disease process. Blocking tissue transglutaminase has the potential to offer patients additional safety when used in conjunction with a ‘largely’ gluten-free diet thereby improving the quality-of-life of millions of people.
The drug candidate ZED1227 is a “first-in-class” compound, meaning it is the first transglutaminase blocker explored in humans. Already in 2011, Dr. Falk Pharma licensed the rights for ZED1227 in Europe and took charge of preclinical and clinical development of the new chemical entity towards a pharmacological agent. In July 2021 Dr. Falk Pharma and Zedira announced the “successful completion of the phase 2a proof of concept study of ZED1227 for the treatment of Celiac Disease”. The detailed results of the study are published in the New England Journal of Medicine
). The press release for an overview can be found here
The proof-of-concept in the study is of vital importance way beyond celiac disease:
The first in class new chemical entity validated TG2 as druggable target. Now, the spotlight focusses on fibrotic disorders and anticoagulation. 1
Büchold C, Hils M, Gerlach U, Weber J, Pelzer C, Heil A, Aeschlimann D, Pasternack R. Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease. Cells. 2022; 11(10):1667. https://doi.org/10.3390/cells11101667